CA2465100A1 - Quinazoline derivatives as antitumor agents - Google Patents

Quinazoline derivatives as antitumor agents Download PDF

Info

Publication number: CA2465100A1
Authority: CA; Canada
Prior art keywords: alkyl; group; formula; amino; yloxy
Prior art date: 2001-11-03
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002465100A

Other languages

English (en)

French (fr)

Inventor

Laurent Francois Andre Hennequin

Jason Grant Kettle

Martin Pass

Robert Hugh Bradbury

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

AstraZeneca AB

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2001-11-03

Filing date

2002-10-31

Publication date

2003-05-15

2002-10-31 Application filed by Individual filed Critical Individual

2003-05-15 Publication of CA2465100A1 publication Critical patent/CA2465100A1/en

Status Abandoned legal-status Critical Current

Links

125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract description 32
239000002246 antineoplastic agent Substances 0.000 title description 2
206010028980 Neoplasm Diseases 0.000 claims abstract description 27
238000004519 manufacturing process Methods 0.000 claims abstract description 17
238000011282 treatment Methods 0.000 claims abstract description 11
238000000034 method Methods 0.000 claims abstract description 9
102000001301 EGF receptor Human genes 0.000 claims abstract description 6
108060006698 EGF receptor Proteins 0.000 claims abstract description 6
230000008569 process Effects 0.000 claims abstract description 6
230000005764 inhibitory process Effects 0.000 claims abstract description 5
239000003814 drug Substances 0.000 claims abstract description 3
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
230000002265 prevention Effects 0.000 claims abstract description 3
-1 cyano, isocyano, nitro, hydroxy, mercapto, amino, formyl Chemical group 0.000 claims description 1745
125000000217 alkyl group Chemical group 0.000 claims description 1322
125000001424 substituent group Chemical group 0.000 claims description 417
229910052739 hydrogen Inorganic materials 0.000 claims description 258
239000001257 hydrogen Substances 0.000 claims description 257
125000000623 heterocyclic group Chemical group 0.000 claims description 224
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 205
125000003545 alkoxy group Chemical group 0.000 claims description 170
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 156
125000005843 halogen group Chemical group 0.000 claims description 147
229910052760 oxygen Inorganic materials 0.000 claims description 146
125000001072 heteroaryl group Chemical group 0.000 claims description 136
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 132
125000003118 aryl group Chemical group 0.000 claims description 131
125000003282 alkyl amino group Chemical group 0.000 claims description 122
229910052757 nitrogen Inorganic materials 0.000 claims description 117
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 116
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 113
125000005236 alkanoylamino group Chemical group 0.000 claims description 105
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 100
125000000304 alkynyl group Chemical group 0.000 claims description 93
125000001589 carboacyl group Chemical group 0.000 claims description 92
125000003342 alkenyl group Chemical group 0.000 claims description 91
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 86
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 84
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 83
125000001153 fluoro group Chemical group F* 0.000 claims description 81
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 74
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 72
229910052717 sulfur Inorganic materials 0.000 claims description 60
125000004414 alkyl thio group Chemical group 0.000 claims description 58
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 57
125000004432 carbon atom Chemical group C* 0.000 claims description 57
125000001309 chloro group Chemical group Cl* 0.000 claims description 55
125000004423 acyloxy group Chemical group 0.000 claims description 52
125000003302 alkenyloxy group Chemical group 0.000 claims description 50
125000005133 alkynyloxy group Chemical group 0.000 claims description 49
150000003839 salts Chemical class 0.000 claims description 49
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 46
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 45
238000003780 insertion Methods 0.000 claims description 43
230000037431 insertion Effects 0.000 claims description 43
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
150000001875 compounds Chemical class 0.000 claims description 42
125000000753 cycloalkyl group Chemical group 0.000 claims description 42
125000004093 cyano group Chemical group *C#N 0.000 claims description 41
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 41
125000003386 piperidinyl group Chemical group 0.000 claims description 40
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 37
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 35
125000000392 cycloalkenyl group Chemical group 0.000 claims description 35
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 34
125000002947 alkylene group Chemical group 0.000 claims description 33
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 30
125000002619 bicyclic group Chemical group 0.000 claims description 29
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 28
125000001246 bromo group Chemical group Br* 0.000 claims description 26
229910002091 carbon monoxide Inorganic materials 0.000 claims description 25
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 25
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 24
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 24
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 23
125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 23
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 23
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 21
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 21
229910052799 carbon Inorganic materials 0.000 claims description 18
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 18
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 17
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 15
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 15
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 14
125000001041 indolyl group Chemical group 0.000 claims description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 11
125000003396 thiol group Chemical class [H]S* 0.000 claims description 11
125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 10
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 10
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 10
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 10
125000002393 azetidinyl group Chemical group 0.000 claims description 10
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 10
125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 9
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 8
241000282414 Homo sapiens Species 0.000 claims description 8
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 7
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 7
125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 7
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 7
125000004430 oxygen atom Chemical group O* 0.000 claims description 7
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 7
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
125000000464 thioxo group Chemical group S=* 0.000 claims description 7
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 6
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 6
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
125000005530 alkylenedioxy group Chemical group 0.000 claims description 5
125000004518 1,2,5-thiadiazol-3-yl group Chemical group S1N=C(C=N1)* 0.000 claims description 4
125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 claims description 4
241001465754 Metazoa Species 0.000 claims description 3
239000002253 acid Substances 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
150000003246 quinazolines Chemical class 0.000 claims 30
150000002431 hydrogen Chemical class 0.000 claims 18
125000000524 functional group Chemical group 0.000 claims 12
238000006243 chemical reaction Methods 0.000 claims 7
125000006239 protecting group Chemical group 0.000 claims 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 3
150000001412 amines Chemical class 0.000 claims 3
230000008878 coupling Effects 0.000 claims 3
238000010168 coupling process Methods 0.000 claims 3
238000005859 coupling reaction Methods 0.000 claims 3
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims 3
125000003277 amino group Chemical group 0.000 claims 2
238000003776 cleavage reaction Methods 0.000 claims 2
230000007017 scission Effects 0.000 claims 2
IWKAXCOAQXMTJI-UHFFFAOYSA-N 2-[3-[4-(3-chloro-4-fluoroanilino)-5-(oxan-4-yloxy)quinazolin-7-yl]oxypropyl-methylamino]ethanol Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OCCCN(CCO)C)=CC=1OC1CCOCC1 IWKAXCOAQXMTJI-UHFFFAOYSA-N 0.000 claims 1
ZUPYBUSTUDADEY-UHFFFAOYSA-N 2-[4-[3-[4-(3-chloro-4-fluoroanilino)-5-(oxolan-3-yloxy)quinazolin-7-yl]oxypropyl]piperazin-1-yl]-n,n-dimethylacetamide Chemical compound C1CN(CC(=O)N(C)C)CCN1CCCOC1=CC(OC2COCC2)=C(C(NC=2C=C(Cl)C(F)=CC=2)=NC=N2)C2=C1 ZUPYBUSTUDADEY-UHFFFAOYSA-N 0.000 claims 1
ZLSSHFKVIJGWSK-UHFFFAOYSA-N 2-[4-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxypiperidin-1-yl]acetamide Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(CC(N)=O)CC1 ZLSSHFKVIJGWSK-UHFFFAOYSA-N 0.000 claims 1
ZCROTVJMBVJMTC-UHFFFAOYSA-N 7-methoxy-5-(1-methylpiperidin-4-yl)oxy-n-[3-methyl-4-(1,3-thiazol-4-ylmethoxy)phenyl]quinazolin-4-amine Chemical compound C=12C(NC=3C=C(C)C(OCC=4N=CSC=4)=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 ZCROTVJMBVJMTC-UHFFFAOYSA-N 0.000 claims 1
AEUSZNVUMDOVLL-UHFFFAOYSA-N 7-methoxy-n-(3-methylphenyl)-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(C)C=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 AEUSZNVUMDOVLL-UHFFFAOYSA-N 0.000 claims 1
LDOXZKYFYSFOSU-UHFFFAOYSA-N 7-methoxy-n-[3-methyl-4-[(5-methyl-1,2-oxazol-3-yl)methoxy]phenyl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(C)C(OCC4=NOC(C)=C4)=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 LDOXZKYFYSFOSU-UHFFFAOYSA-N 0.000 claims 1
101150113809 COQ10 gene Proteins 0.000 claims 1
150000001204 N-oxides Chemical class 0.000 claims 1
230000010933 acylation Effects 0.000 claims 1
238000005917 acylation reaction Methods 0.000 claims 1
150000003973 alkyl amines Chemical class 0.000 claims 1
230000029936 alkylation Effects 0.000 claims 1
238000005804 alkylation reaction Methods 0.000 claims 1
239000003638 chemical reducing agent Substances 0.000 claims 1
239000012024 dehydrating agents‎ Substances 0.000 claims 1
239000003085 diluting agent Substances 0.000 claims 1
125000000468 ketone group Chemical group 0.000 claims 1
QTDOMJNKZTZSNY-UHFFFAOYSA-N n'-[3-[4-(3-chloro-4-fluoroanilino)-5-(oxan-4-yloxy)quinazolin-7-yl]oxypropyl]-n,n,n'-trimethylethane-1,2-diamine Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OCCCN(C)CCN(C)C)=CC=1OC1CCOCC1 QTDOMJNKZTZSNY-UHFFFAOYSA-N 0.000 claims 1
XMVKPIXFNJYUSW-UHFFFAOYSA-N n-(1h-indol-5-yl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C4C=CNC4=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 XMVKPIXFNJYUSW-UHFFFAOYSA-N 0.000 claims 1
ZXNJYEMOJBYQIG-UHFFFAOYSA-N n-(3-bromo-1h-indol-5-yl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C4C(Br)=CNC4=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 ZXNJYEMOJBYQIG-UHFFFAOYSA-N 0.000 claims 1
NFTRWLJBWYWZJH-UHFFFAOYSA-N n-(3-bromophenyl)-7-(2-methoxyethoxy)-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(Br)C=CC=3)=NC=NC2=CC(OCCOC)=CC=1OC1CCN(C)CC1 NFTRWLJBWYWZJH-UHFFFAOYSA-N 0.000 claims 1
IDXSGPFMJYUSNR-HXUWFJFHSA-N n-(3-bromophenyl)-7-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC(OC2CCN(C)CC2)=C(C(NC=2C=C(Br)C=CC=2)=NC=N2)C2=C1 IDXSGPFMJYUSNR-HXUWFJFHSA-N 0.000 claims 1
ZZDLDXZKLALEKT-UHFFFAOYSA-N n-(3-bromophenyl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(Br)C=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 ZZDLDXZKLALEKT-UHFFFAOYSA-N 0.000 claims 1
HPLPZQXVSXASSV-UHFFFAOYSA-N n-(3-chloro-1h-indol-5-yl)-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C4C(Cl)=CNC4=CC=3)=C12 HPLPZQXVSXASSV-UHFFFAOYSA-N 0.000 claims 1
HQPQWDCOALZSAB-UHFFFAOYSA-N n-(3-chloro-1h-indol-5-yl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C4C(Cl)=CNC4=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 HQPQWDCOALZSAB-UHFFFAOYSA-N 0.000 claims 1
ZETIQJIOZJGBJO-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-5-(1-methylpiperidin-4-yl)oxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC(OCCCN2CCCCC2)=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C12 ZETIQJIOZJGBJO-UHFFFAOYSA-N 0.000 claims 1
AYRGEEXLRPTEGW-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-5-(1-methylpiperidin-4-yl)oxy-7-[2-(4-propan-2-ylpiperazin-1-yl)ethoxy]quinazolin-4-amine Chemical compound C1CN(C(C)C)CCN1CCOC1=CC(OC2CCN(C)CC2)=C(C(NC=2C=C(Cl)C(F)=CC=2)=NC=N2)C2=C1 AYRGEEXLRPTEGW-UHFFFAOYSA-N 0.000 claims 1
UZMXZABPDQQTCY-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-5-(oxolan-3-yloxy)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCCC3)=CC(OC3COCC3)=C12 UZMXZABPDQQTCY-UHFFFAOYSA-N 0.000 claims 1
TVIYMNMSDSRYOR-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-(2-methoxyethoxy)-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OCCOC)=CC=1OC1CCN(C)CC1 TVIYMNMSDSRYOR-UHFFFAOYSA-N 0.000 claims 1
KJGAKDILLKUUKR-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-(3-morpholin-4-ylpropoxy)-5-(oxolan-3-yloxy)quinazolin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=CC(OC3COCC3)=C12 KJGAKDILLKUUKR-UHFFFAOYSA-N 0.000 claims 1
PHAHMWKBVJWSRW-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-[3-(4-methylpiperazin-1-yl)propoxy]-5-(oxolan-3-yloxy)quinazolin-4-amine Chemical compound C1CN(C)CCN1CCCOC1=CC(OC2COCC2)=C(C(NC=2C=C(Cl)C(F)=CC=2)=NC=N2)C2=C1 PHAHMWKBVJWSRW-UHFFFAOYSA-N 0.000 claims 1
JJGWQXMAOXKYNE-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 JJGWQXMAOXKYNE-UHFFFAOYSA-N 0.000 claims 1
JFJUDTHJJPEOAI-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-methoxy-5-piperidin-4-yloxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCNCC1 JFJUDTHJJPEOAI-UHFFFAOYSA-N 0.000 claims 1
ZQSVHYHVRLBHRQ-UHFFFAOYSA-N n-(3-chloro-4-phenylmethoxyphenyl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(Cl)C(OCC=4C=CC=CC=4)=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 ZQSVHYHVRLBHRQ-UHFFFAOYSA-N 0.000 claims 1
DPDBPSDRMGEXOE-HXUWFJFHSA-N n-(3-chlorophenyl)-7-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC(OC2CCN(C)CC2)=C(C(NC=2C=C(Cl)C=CC=2)=NC=N2)C2=C1 DPDBPSDRMGEXOE-HXUWFJFHSA-N 0.000 claims 1
KJXIINIUXPYFOR-UHFFFAOYSA-N n-(3-chlorophenyl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(Cl)C=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 KJXIINIUXPYFOR-UHFFFAOYSA-N 0.000 claims 1
XGTYOOCWZXWNGX-UHFFFAOYSA-N n-(3-ethynylphenyl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(C=CC=3)C#C)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 XGTYOOCWZXWNGX-UHFFFAOYSA-N 0.000 claims 1
BTXPGTQGSXUJHB-UHFFFAOYSA-N n-[1-[(2-fluorophenyl)methyl]indol-5-yl]-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C4C=CN(CC=5C(=CC=CC=5)F)C4=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 BTXPGTQGSXUJHB-UHFFFAOYSA-N 0.000 claims 1
ISAVFODCQKKGSP-UHFFFAOYSA-N n-[1-[(3-fluorophenyl)methyl]indol-5-yl]-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C4C=CN(CC=5C=C(F)C=CC=5)C4=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 ISAVFODCQKKGSP-UHFFFAOYSA-N 0.000 claims 1
FEDMNRRTHMURLW-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 FEDMNRRTHMURLW-UHFFFAOYSA-N 0.000 claims 1
230000003647 oxidation Effects 0.000 claims 1
238000007254 oxidation reaction Methods 0.000 claims 1
238000006268 reductive amination reaction Methods 0.000 claims 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Ceramic Engineering (AREA)
Health & Medical Sciences (AREA)
Manufacturing & Machinery (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Inorganic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Structural Engineering (AREA)
Materials Engineering (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA002465100A 2001-11-03 2002-10-31 Quinazoline derivatives as antitumor agents Abandoned CA2465100A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB0126433.2		2001-11-03
GBGB0126433.2A GB0126433D0 (en)	2001-11-03	2001-11-03	Compounds
PCT/GB2002/004932 WO2003040109A2 (en)	2001-11-03	2002-10-31	Quinazoline derivatives as antitumor agents

Publications (1)

Publication Number	Publication Date
CA2465100A1 true CA2465100A1 (en)	2003-05-15

Family

ID=9925096

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002465100A Abandoned CA2465100A1 (en)	2001-11-03	2002-10-31	Quinazoline derivatives as antitumor agents

Country Status (24)

Country	Link
US (2)	US20050054662A1 (is)
EP (1)	EP1444211B1 (is)
JP (1)	JP2005511603A (is)
KR (1)	KR20050042058A (is)
CN (1)	CN1764651A (is)
AR (1)	AR037193A1 (is)
AT (1)	ATE421507T1 (is)
BR (1)	BR0213843A (is)
CA (1)	CA2465100A1 (is)
CO (1)	CO5580775A2 (is)
DE (1)	DE60230995D1 (is)
ES (1)	ES2319880T3 (is)
GB (1)	GB0126433D0 (is)
HU (1)	HUP0401994A2 (is)
IL (1)	IL161620A0 (is)
IS (1)	IS7241A (is)
MX (1)	MXPA04004220A (is)
NO (1)	NO20042288L (is)
NZ (1)	NZ532523A (is)
PL (1)	PL369833A1 (is)
RU (1)	RU2004116908A (is)
TW (1)	TW200302221A (is)
WO (1)	WO2003040109A2 (is)
ZA (2)	ZA200403203B (is)

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2001
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2002
- 2002-10-31 CN CNA028262824A patent/CN1764651A/zh active Pending
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- 2002-10-31 MX MXPA04004220A patent/MXPA04004220A/es unknown
- 2002-10-31 RU RU2004116908/04A patent/RU2004116908A/ru not_active Application Discontinuation
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- 2002-10-31 HU HU0401994A patent/HUP0401994A2/hu unknown
- 2002-10-31 IL IL16162002A patent/IL161620A0/xx unknown
- 2002-10-31 US US10/494,388 patent/US20050054662A1/en not_active Abandoned
- 2002-10-31 ES ES02774961T patent/ES2319880T3/es not_active Expired - Lifetime
- 2002-10-31 KR KR1020047006735A patent/KR20050042058A/ko not_active Withdrawn
- 2002-10-31 AT AT02774961T patent/ATE421507T1/de not_active IP Right Cessation
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- 2002-10-31 WO PCT/GB2002/004932 patent/WO2003040109A2/en not_active Ceased
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- 2002-11-01 AR ARP020104182A patent/AR037193A1/es not_active Application Discontinuation
2004
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- 2004-06-03 NO NO20042288A patent/NO20042288L/no not_active Application Discontinuation
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Publication number	Publication date
EP1444211B1 (en)	2009-01-21
IS7241A (is)	2004-04-30
EP1444211A2 (en)	2004-08-11
US20070088044A1 (en)	2007-04-19
DE60230995D1 (de)	2009-03-12
AR037193A1 (es)	2004-10-27
BR0213843A (pt)	2004-08-31
IL161620A0 (en)	2004-09-27
NO20042288L (no)	2004-06-03
US20050054662A1 (en)	2005-03-10
MXPA04004220A (es)	2004-09-10
GB0126433D0 (en)	2002-01-02
ATE421507T1 (de)	2009-02-15
KR20050042058A (ko)	2005-05-04
HUP0401994A2 (hu)	2005-01-28
TW200302221A (en)	2003-08-01
PL369833A1 (en)	2005-05-02
ES2319880T3 (es)	2009-05-14
HK1065801A1 (en)	2005-03-04
CN1764651A (zh)	2006-04-26
NZ532523A (en)	2007-02-23
CO5580775A2 (es)	2005-11-30
JP2005511603A (ja)	2005-04-28
ZA200403203B (en)	2005-07-28
ZA200403200B (en)	2005-07-28
WO2003040109A2 (en)	2003-05-15
WO2003040109A3 (en)	2003-06-26
RU2004116908A (ru)	2005-11-10

Legal Events

Date	Code	Title	Description
2008-10-31	FZDE	Discontinued

Publication	Publication Date	Title
EP1444211B1 (en)	2009-01-21	Quinazoline derivatives as antitumor agents
EP1444210B1 (en)	2009-02-18	Qunazoline derivatives as antitumor agents
JP5178534B2 (ja)	2013-04-10	キノリン誘導体
EP1631292B1 (en)	2009-08-05	4-anilino-quinazoline derivatives as antiproliferative agents
US20070032513A1 (en)	2007-02-08	Quinazoline derivatives
EP1622620B1 (en)	2008-02-20	Quinazoline derivatives and their use in the treatment of cancer
EP1802591A1 (en)	2007-07-04	Quinazoline derivatives
WO2007099335A1 (en)	2007-09-07	Quinoline derivatives for treating cancer
US20090036485A1 (en)	2009-02-05	Quinoline derivatives
AU2002341158A1 (en)	2003-05-19	Quinazoline derivatives as antitumor agents
HK1065801B (en)	2009-06-26	Quinazoline derivatives as antitumor agents
AU2002341156A1 (en)	2003-05-19	Quinazoline derivatives as antitumor agents
HK1066218B (en)	2009-06-26	Qunazoline derivatives as antitumor agents
HK1087613B (en)	2008-06-20	Quinazoline derivatives and their use in the treatment of cancer
HK1107339B (en)	2012-08-10	Quinazoline derivatives
HK1087632B (en)	2009-12-31	4-anilino-quinazoline derivatives as antiproliferative agents
HK1112462A1 (en)	2008-09-05	Pyrazolopyrimidine compounds as antitumor agents